Even new antibiotics losing effectiveness as bacteria quickly adapt

As more and more bacteria develop resistance to the drugs designed to kill them, a new study has found that even a relatively new antibiotic isn’t immune. Researchers have uncovered a gene amplification mechanism that causes bacteria to become increasingly resistant to the drug albicidin.

Known to be highly effective at killing bacteria, including the superbugs Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus or ‘Golden Staph’), the relatively new antibiotic albicidin was hailed as an answer to the problem of antibiotic resistance.

However, a new study by researchers at Freie Universität Berlin has found that, despite its newness, common – and problematic – bacteria are already developing resistance to albicidin by using a mechanism of gene amplification.

Albicidin has a different mode of action than other antibiotics. Known as a peptide antibiotic, it inhibits DNA gyrase, essential enzymes that help progress bacterial DNA replication. DNA gyrase enzymes are present in bacteria but not humans, making it a good target.

The researchers used a broad set of tools to examine the mechanisms by which bacteria become resistant to albicidin, including RNA sequencing, protein analysis, X-ray crystallography, and molecular modeling. They found that two bacteria commonly associated with infection in humans, Salmonella typhimurium and E. coli, developed resistance to albicidin when exposed to increasingly higher concentrations of the drug.

They found that the source of the resistance was an increase in the number of copies of the gene STM3175 in the bacterial cells, which was amplified in successive generations as the cells multiplied, developing up to a 1,000-fold resistance. The gene encodes a protein that interacts with albicidin, protecting bacteria from it.

The researchers also found that the same resistance mechanism was widespread among both harmless and pathogenic bacteria, including Vibrio vulnificus, which can cause life-threatening wound infections, and Pseudomonas aeruginosa, which can cause pneumonia and blood infections following surgery.

Antibiotic resistance is a matter of increasing concern for public healthcare and, according to the World Health Organization (WHO), one of the biggest threats to global health, food security and development. A 2019 article in the journal The Lancet reported that 1.27 million deaths were attributable to bacterial antimicrobial resistance during that year.

The current study provides a better understanding of the mechanisms underlying bacterial resistance to antibiotics; unfortunately, it’s in relation to a relatively new drug that was touted as being means of addressing said resistance. Nonetheless, the study’s findings could inform the development of albicidin-based antibiotic treatments.

The study was published in the journal PLOS Biology.

Source: Freie Universität Berlin via Scimex

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